Stimulating Neural Activity to Improve Blood Flow and Reduce Amyloid: Path to Clinical Trials (FLICKER)

This is an interventional supportive care trial for Alzheimer Disease Read More

Inclusion Criteria:

• Subjects must have a subjective memory concern as reported by subject, study partner or clinician.
• Meets local criteria for diagnosis of mild cognitive impairment (MCI).
• Montreal Cognitive Assessment (MoCA) score >15. Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI.
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
• General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's Disease (AD) cannot be made by the physician at the time of the screening visit.
• Stable on medications for 4 weeks prior to initiation of study sessions.
• Geriatric Depression Scale (GDS) ≤ than 6.
• Male or female outpatients aged 50-90 (inclusive).
• Able to hear without the use of hearing aids.
• Study partner who lives with the participant and can provide a reliable assessment of the participant's level of function, is available for all clinic visits, and can serve as a supervisor/monitor for the home-based Flicker sessions for the duration of the study.
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
• Able to communicate in English with study personnel.
• Able to understand the nature of the study and provision of written informed consent prior to conduct of any study procedures.
• Willing to undergo repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scans.
• Agrees to blood collection for apolipoprotein E (ApoE) and biomarker testing.
• Agrees to lumbar puncture over the course of the study for the collection of cerebrospinal fluid (CSF).

Exclusion Criteria:

• Any significant neurologic disease other than MCI and suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, poorly controlled seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
• Screening/baseline MRI scan with evidence of infection, large vessel infarction or other focal structural lesions that could account for the memory deficits. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
• Contraindication to MRI due to pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, or excessive weight.
• Presence of clinically significant suicide risk, based on the Investigator's judgment informed by a structured clinician interview. Any suicide attempt within the past 1 year of the screening visit is exclusionary.
• Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders-4 (DSM-IV) within the past 1 year, or history of schizophrenia.
• Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
• History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria).
• Known history of epilepsy or migraines, which may be exacerbated by study intervention.
• History of narrow angle (acute angle) glaucoma.
• Current use of warfarin or other blood thinners (exclusionary for lumbar puncture).
• Inability to obtain initial CSF sample.
• Current use of Namenda (memantine).
• Current use of medications that lower seizure threshold, including Wellbutrin, Ciprofloxacin, Levofloxacin, Seroquel, Phenergan, and Sumatriptan.
• Current use of anti-psychotic medication.
• CSF profile inconsistent with underlying Alzheimer's Disease pathology.
• Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the investigator, prohibits enrollment of subject into the study.
• Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director.